Alcohol Abuse, Alcoholism, Bipolar Disorder
Conditions
Keywords
Alcohol Use Disorder, Bipolar Disorder, Mood, Alcohol Craving, Aripiprazole, Schizoaffective Disorder
Brief summary
The investigators will conduct a 12-week, randomized, double-blind, parallel-group, placebo-controlled study of aripiprazole in 132 persons with Alcohol Use Disorder (AUD) and bipolar I or II disorder, currently depressed or mixed phase. Primary Aim will be to assess change in alcohol use by the Timeline Followback (TLFB) method. Secondary Aim will include change in alcohol craving using the Penn Alcohol Craving Scale (PACS). Changes in psychiatric symptoms (mania/hypomania and depression) and predictors of response will be assessed. Participants with ≥ 1 drinking day at week 12 will be enrolled in a 4-week extension phase with an upward titration to 30 mg/day for those in the active treatment group. The placebo group will remain on placebo. Subjects will be discontinued from the study if any of the following conditions occurs: change in diagnosis to other than bipolar I or II disorder and AUD, development of active suicidal or homicidal ideation with plan and intent, worsening in mood symptoms, that in the opinion of the investigators requires discontinuation, pregnancy, development of severe or life-threatening medical condition, involuntary psychiatric hospitalization or incarceration, significant alcohol withdrawal (e.g. delirium tremens) based on clinical judgment (increases in Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scores will initiate a careful clinical assessment of possible worsening of withdrawal symptoms), or cocaine or amphetamine-positive urine drug screen during the study.
Interventions
DRUGAripiprazole
Aripiprazole is an atypical antipsychotic drug that is used to treat mental/mood disorders. It works to restore the balance of neurotransmitters.
DRUGPlacebo
Inactive ingredient matching the active comparators in appearance.
Sponsors
University of Texas Southwestern Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Outpatient men and women age 18-65 years old with bipolar I, II, Not Otherwise Specified (NOS) disorder, or Schizoaffective Bipolar Type * If diagnosed with Bipolar I, Bipolar NOS w/history of mania or Schizoaffective Disorder Bipolar Type, current mood stabilizer therapy (lithium, valproic acid, lamotrigine, gabapentin) with stable dose for \> 28 days prior to randomization. * Baseline Barrett Impulsiveness Scale-11 Score of \> 62 (above average impulsivity) * Systolic BP \> 100 and \< 165 and Diastolic BP \> 60 and \< 105 with no evidence of orthostatic hypotension * Current Diagnosis of Alcohol Use Disorder with at least moderate severity * Alcohol use of an average of 15 drinks per 7 days in the past 28 days prior to intake for men, and an average of 8 drinks per 7 day period in the past 28 days prior to intake for women * Current mood stabilizer therapy with stable dose for \> 28 days * Fluent in English or Spanish
Exclusion criteria
* Baseline Hamilton Rating Scale for Depression (HRSD) or Young Mania Rating Scale (YMRS) scores \> 35 * Mood disorders other than bipolar I, II, NOS or schizoaffective disorder bipolar type (e.g. cyclothymic disorders, schizophrenia, schizoaffective disorder depressive type, or unipolar depression based on the SCID), other disorders, e.g. anxiety disorders, will be allowed. * Current diagnosis of amphetamine or cocaine use disorder or a cocaine or amphetamine positive baseline urine sample. * Evidence of clinically significant alcohol withdrawal symptoms * Current treatment with an atypical antipsychotic * Current treatment with naltrexone, acamprosate, disulfiram, or topiramate in the last 28 days * Prior treatment with Aripiprazole within the last year or lifetime history of intolerable side effects to Aripiprazole * Vulnerable populations (e.g. pregnant, nursing, cognitively impaired, incarcerated.) * Evidence of clinically significant alcohol withdrawal symptoms defined as a CIWA-Ar score of ≥ 10. * High risk for suicide * Aspartate Amino Transferase (AST) or Alanine Amino Transferase (ALT) \> 3 times upper limit of normal * Current use of Cytochrome P450 3A4 inducing medication (e.g. carbamazepine, rifabutin, rifampin, ritonavir). * Use of other substances (besides cocaine/amphetamine) is allowed if the use disorder is no greater than moderate severity and alcohol is the self-identified substance of choice. * History of neuroleptic malignant syndrome or tardive dyskinesia. More specific inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Timeline Follow Back (TLFB) | 12 weeks | The Timeline Followback (TLFB) is used to assess recent alcohol use (and if present, other substance use). The calculation is based on the change between baseline and week 12. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aripiprazole Aripiprazole will be given to the participant beginning at 2 mg per day(QD) then titrating up to 5 mg QD at week 1, 10 mg QD at week 2, 15 mg QD at week 3 until the end of the preliminary phase. If the participant qualifies for the extension phase, then they will be titrated up again at week 12 to 30 mg QD.
Aripiprazole: Aripiprazole is an atypical antipsychotic drug that is used to treat mental/mood disorders. It works to restore the balance of neurotransmitters. | 36 |
| Placebo Matching placebo will be given to the participant beginning at 2mg QD then titrating up to 5 mg QD at week 1, 10 mg QD at week 2, 15 mg QD at week 3 until the end of the preliminary phase. If the participant qualifies for the extension phase, then they will be titrated up again at week 12 to 30 mg QD.
Placebo: Inactive ingredient matching the active comparators in appearance. | 39 |
| Total | 75 |
Baseline characteristics
| Characteristic | Aripiprazole | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 43.71 years STANDARD_DEVIATION 9.35 | 43.58 years STANDARD_DEVIATION 12.25 | 43.65 years STANDARD_DEVIATION 10.84 |
| BIS-11 | 79.09 units on a scale STANDARD_DEVIATION 13.41 | 78.10 units on a scale STANDARD_DEVIATION 13.34 | 78.56 units on a scale STANDARD_DEVIATION 13.29 |
| CIWA-Ar | 2.50 units on a scale STANDARD_DEVIATION 2.67 | 3.05 units on a scale STANDARD_DEVIATION 3.6 | 2.79 units on a scale STANDARD_DEVIATION 3.18 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 7 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants | 28 Participants | 55 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 4 Participants | 8 Participants |
| HRSD | 13.62 units on a scale STANDARD_DEVIATION 7.4 | 14.19 units on a scale STANDARD_DEVIATION 7.56 | 13.82 units on a scale STANDARD_DEVIATION 7.43 |
| IDS-SR | 26.03 units on a scale STANDARD_DEVIATION 15.79 | 30.62 units on a scale STANDARD_DEVIATION 15.42 | 28.42 units on a scale STANDARD_DEVIATION 15.66 |
| PACS | 19.50 units on a scale STANDARD_DEVIATION 6.31 | 17.79 units on a scale STANDARD_DEVIATION 7.53 | 18.60 units on a scale STANDARD_DEVIATION 6.98 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 20 Participants | 34 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 20 Participants | 15 Participants | 35 Participants |
| Sex: Female, Male Female | 16 Participants | 19 Participants | 35 Participants |
| Sex: Female, Male Male | 20 Participants | 20 Participants | 40 Participants |
| TLFB (Drinks per Drinking Day) | 8.42 standard drinks per drinking day STANDARD_DEVIATION 5.12 | 10.02 standard drinks per drinking day STANDARD_DEVIATION 7.94 | 9.25 standard drinks per drinking day STANDARD_DEVIATION 6.74 |
| YMRS | 8.92 units on a scale STANDARD_DEVIATION 6.8 | 10.33 units on a scale STANDARD_DEVIATION 6.96 | 9.85 units on a scale STANDARD_DEVIATION 7.34 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 36 | 0 / 39 |
| other Total, other adverse events | 13 / 36 | 5 / 39 |
| serious Total, serious adverse events | 0 / 36 | 2 / 39 |
Outcome results
Primary
Timeline Follow Back (TLFB)
The Timeline Followback (TLFB) is used to assess recent alcohol use (and if present, other substance use). The calculation is based on the change between baseline and week 12.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole | Timeline Follow Back (TLFB) | -0.82 drinks per drinking day | Standard Deviation 5.86 |
| Placebo | Timeline Follow Back (TLFB) | -0.71 drinks per drinking day | Standard Deviation 4.23 |